Intrinsic Disorder in Ubiquitination Substrates
Intrinsic Disorder in Ubiquitination Substrates
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DOI：
10.1016/j.jmb.2011.07.024
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发表时间：
2011-09-23
影响因子：
5.6
通讯作者：
Levy, Yaakov
中科院分区：
文献类型：
--
作者：
Hagai, Tzachi;Azia, Ariel;Levy, Yaakov
泛素-蛋白酶体系统负责真核生物中大量蛋白质的降解。降解是许多细胞途径中的一个基本过程，涉及蛋白酶体降解各种不相关的底物，同时保持其破坏目标的特异性，并避免不必要的蛋白分解。蛋白酶体如何完成这一任务是深入研究的主题。许多蛋白质是通过共价连接到多泛素链上而被降解的。一些研究已经表明无序区域对于有效降解的重要性。在这里，我们分析了482个体内泛素化底物的数据集和一个已知泛素化介导降解的子集。我们发现，与磷酸化位点和其他调节区相比，泛素化位点并不倾向于位于无序区域，并且大量底物在结构区域被修饰。在降解介导的泛素化中，泛素化位点存在明显的偏向，位于无序区；然而，仍有相当数量的泛素化位点在有序区被发现。此外，在许多情况下，泛素化底物中没有无序区域或远离修饰区域。这些令人惊讶的发现提出了一个问题，即这些蛋白质是如何被蛋白酶体成功地展开并最终被降解的。它们表明折叠的结构域一定受到一些额外因素的干扰，如p97复合体，或者泛素化可能导致展开。(C)2011爱思唯尔有限公司。保留所有权利。
The ubiquitin-proteasome system is responsible for the degradation of numerous proteins in eukaryotes. Degradation is an essential process in many cellular pathways and involves the proteasome degrading a wide variety of unrelated substrates while retaining specificity in terms of its targets for destruction and avoiding unneeded proteolysis. How the proteasome achieves this task is the subject of intensive research. Many proteins are targeted for degradation by being covalently attached to a polyubiquitin chain. Several studies have indicated the importance of a disordered region for efficient degradation. Here, we analyze a data set of 482 in vivo ubiquitinated substrates and a subset in which ubiquitination is known to mediate degradation. We show that, in contrast to phosphorylation sites and other regulatory regions, ubiquitination sites do not tend to be located in disordered regions and that a large number of substrates are modified at structured regions. In degradation-mediated ubiquitination, there is a significant bias of ubiquitination sites to be in disordered regions; however, a significant number is still found in ordered regions. Moreover, in many cases, disordered regions are absent from ubiquitinated substrates or are located far away from the modified region. These surprising findings raise the question of how these proteins are successfully unfolded and ultimately degraded by the proteasome. They indicate that the folded domain must be perturbed by some additional factor, such as the p97 complex, or that ubiquitination may induce unfolding. (C) 2011 Elsevier Ltd. All rights reserved.